title: Genome-wide association study on serum alkaline phosphatase levels in a Chinese population.
abstract: BACKGROUND
  Serum alkaline phosphatase (ALP) is a complex phenotype influenced by both genetic and environmental factors. Recent Genome-Wide Association Studies (GWAS) have identified several loci affecting ALP levels; however, such studies in Chinese populations are limited. We performed a GWAS analyzing the association between 658,288 autosomal SNPs and serum ALP in 1,461 subjects, and replicated the top SNPs in an additional 8,830 healthy Chinese Han individuals. The interactions between significant locus and environmental factors on serum ALP levels were further investigated.
  
  
  RESULTS
  The association between ABO locus and serum ALP levels was replicated (P = 2.50 × 10⁻²¹, 1.12 × 10⁻⁵⁶ and 2.82 × 10⁻²⁷ for SNP rs8176720, rs651007 and rs7025162 on ABO locus, respectively). SNP rs651007 accounted for 2.15% of the total variance of serum ALP levels independently of the other 2 SNPs. When comparing our findings with previously published studies, ethnic differences were observed across populations. A significant interaction between ABO rs651007 and overweight and obesity was observed (FDR for interaction was 0.036); for individuals with GG genotype, those with normal weight and those who were overweight or obese have similar serum ALP concentrations; minor allele A of rs651007 remarkably reduced serum ALP levels, but this effect was attenuated in overweight and obese individuals.
  
  
  CONCLUSIONS
  Our findings indicate that ABO locus is a major determinant for serum ALP levels in Chinese Han population. Overweight and obesity modifies the effect of ABO locus on serum ALP concentrations.
authors.affiliation: MOE Key Lab of Environment and Health, School of Public Health, Tongji Medical College, Huazhong University of Science & Technology, 430030 Wuhan, Hubei, China. hemeian@hotmail.com.
authors.forename: Jun
authors.initials: J
authors.lastname: Li
authors.forename: Lixuan
authors.initials: L
authors.lastname: Gui
authors.forename: Chen
authors.initials: C
authors.lastname: Wu
authors.forename: Yunfeng
authors.initials: Y
authors.lastname: He
authors.forename: Li
authors.initials: L
authors.lastname: Zhou
authors.forename: Huan
authors.initials: H
authors.lastname: Guo
authors.forename: Jing
authors.initials: J
authors.lastname: Yuan
authors.forename: Binyao
authors.initials: B
authors.lastname: Yang
authors.forename: Xiayun
authors.initials: X
authors.lastname: Dai
authors.forename: Qifei
authors.initials: Q
authors.lastname: Deng
authors.forename: Suli
authors.initials: S
authors.lastname: Huang
authors.forename: Lei
authors.initials: L
authors.lastname: Guan
authors.forename: Die
authors.initials: D
authors.lastname: Hu
authors.forename: Siyun
authors.initials: S
authors.lastname: Deng
authors.forename: Tian
authors.initials: T
authors.lastname: Wang
authors.forename: Jiang
authors.initials: J
authors.lastname: Zhu
authors.forename: Xinwen
authors.initials: X
authors.lastname: Min
authors.forename: Mingjian
authors.initials: M
authors.lastname: Lang
authors.forename: Dongfeng
authors.initials: D
authors.lastname: Li
authors.forename: Handong
authors.initials: H
authors.lastname: Yang
authors.forename: Frank B
authors.initials: FB
authors.lastname: Hu
authors.forename: Dongxin
authors.initials: D
authors.lastname: Lin
authors.forename: Tangchun
authors.initials: T
authors.lastname: Wu
authors.forename: Meian
authors.initials: M
authors.lastname: He
mesh_terms: D000469:Alkaline Phosphatase / Q000097:blood* / Q000235:genetics*; D044466:Asian People / Q000235:genetics*; D002681:China; D002899:Chromosomes, Human, Pair 9 / Q000235:genetics; D005006:Ethnicity / Q000235:genetics; D005260:Female; D059647:Gene-Environment Interaction; D018740:Genetic Heterogeneity; D020022:Genetic Predisposition to Disease; D055106:Genome-Wide Association Study; D006801:Humans; D008297:Male; D008875:Middle Aged; D009765:Obesity / Q000235:genetics; D020641:Polymorphism, Single Nucleotide
chemical_list: D000469:Alkaline Phosphatase